In vivo hematopoietic stem cell modification by mRNA delivery

Breda L, Papp TE, Triebwasser MP, Yadegari A, Fedorky MT, Tanaka N, Abdulmalik O, Pavani G, Wang Y, Grupp SA, Chou ST, Ni H, Mui BL, Tam YK, Weissman D, Rivella S, Parhiz H. Science. 2023 Jul 28; 381(6656): 436-443. doi: 10.1126/science.ade6967. Epub 2023 Jul 27. PMID: 37499029.


Read the Penn Medicine press release: Penn Medicine and CHOP Researchers Develop 'In Vivo' RNA-based Gene Editing Model for Blood Disorders

Editor's Summary, as included in Science

"Bone marrow stem cells are the source of all hematopoietic (blood) cells in the body. For patients with blood disorders, bone marrow transplantation with healthy donor marrow can be a highly successful therapy and can be curative for certain conditions. Breda et al. designed a strategy to reprogram bone marrow stem cells directly within the body without the need for donor cells or the use of potentially toxic conditioning regimens such as chemotherapy or radiation (see the Perspective by Ferrari and Naldini). Messenger RNA was delivered to bone marrow stem cells by intravenous injection in lipid nanoparticles, facilitating both gene editing and bone marrow transplantation. The ability to engineer bone marrow cells inside a patient without the need for traditional transplantation approaches could hold promise for a number of genetic disorders. — Priscilla N. Kelly"